Lambert-Eaton myasthenic syndrome !

An autoimmune disease of the nerve-muscle junction that weakens the hips and shoulders. It is often the first sign of small cell lung cancer.

Updated 2026-11-01

Structures involved

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In histology

Neuromuscular junction: motor end plate and acetylcholine receptors

Why it happens

What it is

An autoimmune disorder in which antibodies against presynaptic voltage-gated calcium channels reduce acetylcholine release at the neuromuscular junction. It causes proximal limb weakness, reduced reflexes and autonomic symptoms, and about half of cases are paraneoplastic.

Who gets it

Rare, much less common than myasthenia gravis. The paraneoplastic form mainly affects middle-aged and older smokers with small cell lung cancer; the non-paraneoplastic form can occur at any age and is associated with other autoimmune diseases. In Latin America, as elsewhere, it is under-recognized and often first labelled as myasthenia gravis or a myopathy.

Causes

Antibodies against P/Q-type voltage-gated calcium channels on the presynaptic nerve terminal
Paraneoplastic: small cell lung cancer expresses the same calcium channels and triggers the immune response
Non-paraneoplastic: autoimmune, associated with other autoimmune diseases and certain HLA types

Risk factors

Smoking (risk of small cell lung cancer)
Age over 50
Personal or family history of autoimmune disease

Pathophysiology

Antibodies block presynaptic calcium channels, so less calcium enters the nerve terminal and fewer vesicles of acetylcholine are released. Each nerve impulse produces a small end-plate potential, causing weakness and low reflexes. With repeated or sustained contraction, calcium builds up in the terminal and release improves, which explains the temporary increase in strength and reflexes after brief exercise (facilitation). The same failure at autonomic synapses causes dry mouth, constipation and erectile dysfunction.

Classification

Paraneoplastic (cancer-associated, mostly small cell lung cancer)
Non-paraneoplastic (primary autoimmune)

Symptoms and signs

Proximal leg weakness first (difficulty climbing stairs or rising from a chair), then proximal arm weakness
Strength and reflexes improve briefly after exercise
Reduced or absent tendon reflexes
Dry mouth, constipation, erectile dysfunction and orthostatic dizziness (autonomic involvement)
Mild ptosis or double vision in some patients, less prominent than in myasthenia gravis
Fatigue; weight loss or cough when a lung tumour is present

Diagnosis

Clinical: Triad of proximal weakness, reduced reflexes and autonomic symptoms. Post-exercise facilitation of strength or reflexes is a useful bedside sign.
Tests: Antibodies against P/Q-type voltage-gated calcium channels are positive in most patients. Repetitive nerve stimulation at high frequency or after brief maximal exercise shows a marked increase in the compound muscle action potential (incremental response); low-frequency stimulation shows a decrement.
Imaging: Chest CT (and PET-CT if negative) to look for small cell lung cancer, with repeated screening for about two years if the first search is negative.

Differential diagnosis

Myasthenia gravis (ocular and bulbar onset, worsens with exercise, preserved reflexes)
Inflammatory myopathy
Botulism (descending paralysis, prominent cranial nerve signs)
Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy
Amyotrophic lateral sclerosis

Goal of treatment

Find and treat any underlying cancer, improve neuromuscular transmission, and suppress the autoimmune response when symptoms persist.

Treatment

Medical: Treatment of the underlying small cell lung cancer (chemotherapy, radiotherapy), which often improves the weakness.
Medical: Amifampridine (3,4-diaminopyridine), a potassium channel blocker that prolongs nerve depolarization and increases acetylcholine release, is first-line symptomatic therapy; cholinesterase inhibitors give a modest extra effect.
Medical: Immunosuppression with corticosteroids and steroid-sparing agents (e.g. azathioprine) for persistent disease; intravenous immunoglobulin or plasma exchange for severe weakness.
Follow-up: Monitoring of respiratory function and swallowing, review of all drugs that can worsen neuromuscular transmission, and warning the anaesthesia team before surgery.

Complications

Respiratory failure (uncommon)
Prolonged paralysis after neuromuscular blocking agents
Falls from proximal weakness
Complications of the associated lung cancer

Prognosis

Depends mostly on the cancer. In the non-paraneoplastic form, symptoms are usually controlled with treatment and life expectancy is near normal. Patients with Lambert-Eaton and small cell lung cancer may have a somewhat better cancer survival than those without it.

Test yourself

Think of the answer, then tap the question to see it.

Against which channel are the antibodies in Lambert-Eaton syndrome directed?

Presynaptic P/Q-type voltage-gated calcium channels.

Which cancer is most often associated with Lambert-Eaton syndrome?

Small cell lung cancer.

How does strength change with repeated effort in Lambert-Eaton compared with myasthenia gravis?

It improves briefly after exercise in Lambert-Eaton, whereas it worsens with exercise in myasthenia gravis.

What does high-frequency repetitive nerve stimulation show in Lambert-Eaton?

An incremental response: a large increase in the compound muscle action potential.

Which drug is first-line symptomatic treatment and how does it work?

Amifampridine; it blocks presynaptic potassium channels, prolonging depolarization and increasing acetylcholine release.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Lambert-Eaton myasthenic syndrome: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

Vastus lateralis highlighted on the Durgical 3D model